Upon implantation, synthetic materials elicit an inflammatory response that results in a foreign body reaction and fibrous encapsulation. The foreign body reaction severely limits device integration and in vivo performance of numerous biomedical devices, including chemical biosensors, electrical leads/electrodes, therapeutic delivery systems, and orthopaedic and cardiovascular prostheses. Extensive efforts have concentrated on surface treatments and coatings to improve host tissue-implant integration. For instance, current orthopaedic and dental implant surface technologies focus on rough/porous coatings for bone ingrowth and bone-bonding ceramic coatings to promote integration with the surrounding bone. However, while these approaches are generally successful, they can be restricted by slow rates of osseointegration and poor mechanical anchorage in challenging clinical cases, such as those associated with large bone loss and poor bone quality. Since the extracellular matrix controls cell adhesion and function, recent biomimetic strategies have focused on the immobilization of matrix components, including native proteins, peptide sequences, or synthetic derivatives based on matrix molecules. Full-length extracellular matrix proteins are attractive biomimetic targets for functionalizing orthopaedic implant surfaces in order to promote healing, bone formation, and implant fixation. However, these full-length protein strategies are limited by lack of specificity for particular cellular receptors and downstream signaling events and thus allow minimal control over cell and tissue responses. In addition, native ECM proteins often have binding sites for other ligands, such as fibrinogen or von Willebrand factor. Such ligands trigger separate signaling cascades that may ultimately confound phenotypic responses and interfere with controlled cell function.
The most common peptide-based strategy involves the surface deposition of peptides containing the Arg-Gly-Asp (RGD) sequence, which mediates cell attachment to several matrix proteins, including fibronectin, vitronectin, osteopontin, and bone sialoprotein. However, these bio-inspired strategies have yielded marginal increases in implant integration and mechanical fixation. Because RGD is recognized by a large number of integrins in numerous cell types, this approach lacks specificity for particular targeted integrin signaling events and results in non-discriminatory attachment of cells to the RGD-coated surfaces.
Therefore, it is an object of the invention to provide methods and compositions to improve implant integration in vivo.
It is still another object to provide devices and implants coated with biomolecular compositions for increasing tissue integration of the device.
It is yet another object to provide methods and compositions for treating bone defects, bone disorders, or diseases of the bone.